title: Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury.
abstract: Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA values were increased in association with renal dysfunction. Renal ADMA was correlated with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. An antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion-injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus, ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression and cause ADMA accumulation, which may contribute to capillary loss and tubular necrosis in the kidney.
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Obara
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ando
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kaida
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Iwatani
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kaifu
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yokoro
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Toyonaga
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Kusumoto
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fukami
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Okuda
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000581:Amidohydrolases / Q000032:analysis; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D000581:Amidohydrolases; C059999:dimethylargininase; D000111:Acetylcysteine